Genetics of Parkinson's disease: a review of SNCA and LRRK2.

Parkinson's disease (PD) is a common neurodegenerative disorder that usually affects the elderly. Resting tremor, rigidity, bradykinesia, and postural instability are the main symptoms of PD. The loss of dopaminergic neurons in the substantia nigra and Lewy bodies in remaining neurons are pathological characteristics of PD. To combat these symptoms, dopaminergic therapy can benefit PD patients; however, it is only symptomatic therapy. Although the pathogenesis of PD has yet to be elucidated, approximately 10% of PD patients have familial history of PD. Since the first discovery of a causative gene of PD, SNCA, in 1997, 18 other genes have been identified in familial PD. These discoveries make it possible to begin to understand the pathogenesis of PD and can lead to the development of curative therapies. Here, we describe the clinical and pathological features of PD caused by mutations in two major PD-associated genes, SNCA and LRRK2. Mutations in SNCA revealed the pathological association between α-synuclein and PD, while LRRK2 is the most common genetic cause of PD. The patients with LRRK2 mutations present with relatively typical PD phenotypes, but heterogeneous pathologies including α-synuclein, tau, and occasionaly transactive response DNA-binding protein 43.